One of the major hypotheses for tumor promotion proposes that promoters function principally to stimulate proliferation of initiated cell populations which produces either 1) clonal selection of laten tumor cells or 2) increased probability of chromosomal events such as gene rearrangements or fixation of DNA damage. Recent work in our laboratory suggests that the promoting activity of phorol esters in JB6 cells is not due to a promoter-increased rate of cell division. This conclusion derives from two lines of evidence. The first is that when JB6 cells are exposed to promoter under conditions in which they cannot undergo promoter-dependent mitogenesis, promotion of tumor cell phenotype is not inhibited. The second is that variants of promotable JB6 cells which have been selected for resistance to the mitogenic activity of the phorbol ester TPA have been found to retain promotability, thus ruling out mitogenic stimulation as a required event in promotion of transformation in JB6 cells. These TPA mitogen-resistant variants are currently being used to discover biochemical events which determine the mitogenic response.